IMMU-06. REDUCTION OF CD4+ T CELLS NEGATIVELY AFFECTS SURVIVAL IN OLD BUT NOT YOUNG MICE WITH GLIOBLASTOMA

Abstract

Abstract OBJECTIVE Previous work indicates poorer survival outcomes for older glioblastoma (GBM) patients ≥ 65 years of age as compared to younger patients < 65 years of age. The cellular mechanisms associated with this age-dependent survival difference remain elusive. Here we evaluated the overall survival of young and old immunocompetent mice with intracranial brain tumors that were depleted for specific immune cell populations. METHODS Young 6-8 weeks of age vs old 80+ weeks of age C57BL/6 mice were treated for up to 3 weeks with either IgG isotype control antibodies or with depleting antibodies against murine CD4, CD8, or NK1.1, beginning at 3 days prior to- and every 3 days post-intracranial injection of the mouse brain tumor cell lines, GL261 or CT-2A. Overall survival was compared between groups. Additionally, absolute peripheral blood mononuclear cell (PBMC) counts for CD3+ T cells, CD4+ T cells, and CD8+ T cells were analyzed between aneurysm control- and GBM-patients. RESULTS Older adult mice, but not younger mice, with either intracranial GL261 or CT-2A cell-based brain tumors have a significantly decreased overall survival when depleted for CD4+ T cells as compared to the IgG control-treated group, as well as groups depleted for CD8+ T- or NK-cells (P < 0.05). Coincidently, older GBM patients have fewer CD4+ T cells as compared to younger GBM patient counterparts (P < 0.05). CONCLUSIONS The data suggest that the levels of CD4+ T cells play more important roles in the survival of old subjects with GBM than in the younger subjects. A mechanistic understanding for this CD4+ T cell-dependent survival benefit is ongoing.